We are studying the mechanism by which E. coli controls proteins synthesis and messenger RNA degradation in response to changes in growth rate. Our previous work had shown that sudden decreases in growth rate (shift-down) leads to a decreased rate of translational initiation and a stabilization of general mRNA. The most dramatic consequence of this control is the accumulation of 70S "initiation monosomes". Present studies are directed to the following objectives: 1. To determine whether and to what extent control of translational initiation contributes to the regulation of protein synthesis at very slow growth rates. 2. The proteins of the initiation monosomes are being studied in order to determine which step of the ordered sequence of initiation factor reactions has been slowed as a result of the shift-down. 3. We are studying the regions of mRNA which are bound to the "initiation monosomes" in an attempt to determine whether a heterogeneous E. coli mRNA population has any common sequence features which contribute to mRNA-ribosome interaction. 4. We are attempting to determine if there is a general correlation between the length of a mRNA and its functional lifetime. Also, using the ribosome-bound mRNA fragments as a substrate for assay, we are seeking a specific endonuclease which attacks such sites. 5. We are exploring the physiological parameters of growth rate changes involving a variety of carbon sources, to see if E. coli alters macromolecular synthesis in different ways in response to physiologically distinct kinds of stress. We are also studying the possible role of the relA and spoT genes in these stress responses.